CN111919106A

CN111919106A - Biological substance measuring device

Info

Publication number: CN111919106A
Application number: CN201880091036.1A
Authority: CN
Inventors: 小川新平
Original assignee: Mitsubishi Electric Corp
Current assignee: Mitsubishi Electric Corp
Priority date: 2018-03-15
Filing date: 2018-10-29
Publication date: 2020-11-10
Anticipated expiration: 2038-10-29
Also published as: WO2019176157A1; CN111919106B; US20200408686A1; US11408824B2; DE112018007282T5

Abstract

Provided is a noninvasive biological material measuring device capable of measuring the amount of a biological material stably and with high accuracy. A biological substance measurement device (80) is provided with: a first light source (32) that emits first light; an ATR prism (20) having a front surface and a back surface, wherein the first light incident from one end transmits through the inside and exits from the other end; a doubly curved metamaterial layer (90) having a front surface and a back surface, and disposed in back-contact on the front surface of the ATR prism (20); and a first light detector (30) that detects the first light emitted from the ATR prism (20) and measures the amount of the biological substance in the living body from the detected first light.

Description

Biological substance measuring device

Technical Field

The present invention relates to a biological substance measuring apparatus, and more particularly to a biological substance measuring apparatus for measuring a biological substance such as sugar present in a living body by using infrared light.

Background

As a biological substance measurement device for measuring a component of a substance in a living body such as blood glucose, there are an invasive measurement device using puncture or blood collection and a non-invasive measurement device not using the same. A blood glucose level measuring apparatus (blood glucose sensor) used in daily life is desired to be a noninvasive measuring apparatus for alleviating pain of a patient. As a noninvasive blood glucose level measuring apparatus, a sensor using infrared light that can detect a fingerprint spectrum of glucose is considered. For example, patent document 1 discloses the following blood glucose level sensor: in this blood glucose level sensor, infrared light is reflected multiple times in the prism, and the attenuation rate of infrared light by surface plasmon resonance is increased, thereby increasing the sensitivity of the sensor (see [0057], for example).

Documents of the prior art

Patent document

Patent document 1: japanese patent laid-open publication No. 2012 and 070907

Disclosure of Invention

Problems to be solved by the invention

However, infrared light is absorbed in large amounts by water in the skin, and thus reaches only the skin surface. Therefore, the conventional techniques cannot significantly distinguish between the effect of infrared light absorption by glucose or other sugars in the skin and the effect of infrared light absorption by water, and cannot obtain a good Signal-to-Noise ratio (SN ratio). Therefore, it is impossible to measure the blood glucose level stably and with high accuracy.

Accordingly, an object of the present invention is to obtain a noninvasive biological material measurement device capable of measuring the amount of a biological material stably and with high accuracy.

Means for solving the problems

One aspect of the present invention provides a biological material measurement device including: a first light source that emits first light; an ATR prism having a front surface and a back surface, the first light incident from one end being transmitted through the inside and being emitted from the other end; a doubly curved metamaterial layer having a surface and a back surface, disposed in back-contact on the surface of the ATR prism; and a first photodetector for detecting the first light emitted from the ATR prism and measuring the amount of the biological substance in the living body from the detected first light.

ADVANTAGEOUS EFFECTS OF INVENTION

According to the present invention, a noninvasive biological material measuring apparatus capable of measuring the amount of a biological material stably and with high accuracy can be obtained.

Drawings

Fig. 1 is a schematic diagram showing an example of use of a noninvasive blood glucose level measuring apparatus according to embodiment 1 of the present invention.

Fig. 2 is a schematic diagram showing the configuration of a noninvasive blood glucose level measuring apparatus according to embodiment 1 of the present invention.

Fig. 3 is a schematic cross-sectional view of an example of a hyperbolic metamaterial for a noninvasive blood glucose level measuring apparatus according to embodiment 1 of the present invention.

Fig. 4 is a schematic cross-sectional view of another example of the doubly curved metamaterial according to the noninvasive blood glucose level measuring apparatus of embodiment 1 of the present invention.

Fig. 5a is a schematic plan view of another example of the doubly curved metamaterial for a noninvasive blood glucose level measuring apparatus according to embodiment 1 of the present invention.

Fig. 5b is a perspective view illustrating the doubly curved metamaterial of fig. 5 a.

Fig. 5c is a partial cross-sectional perspective view of the doubly curved metamaterial of fig. 5 b.

Fig. 6 is a schematic plan view of another example of the doubly curved metamaterial for a noninvasive blood glucose level measuring apparatus according to embodiment 1 of the present invention.

FIG. 7 shows the vertical axis k_zLet the horizontal axis be k_xA graph showing a dispersion relation of a normal substance.

FIG. 8 shows the vertical axis k_zLet the horizontal axis be k_xA graph showing a dispersion relation of the hyperbolic metamaterial.

Fig. 9 is a schematic diagram showing the optical paths of infrared light and evanescent waves traveling in an ATR prism, a doubly curved metamaterial, and skin.

Fig. 10 is a diagram showing an absorption spectrum of infrared light generated by sugar.

Fig. 11 is a perspective view showing an example of the configuration of an infrared photodetector of a noninvasive blood glucose level measuring apparatus according to embodiment 1 of the present invention.

Fig. 12 is a plan view of an optical element of an infrared light detector of a noninvasive blood glucose level measuring apparatus according to embodiment 1 of the present invention.

Fig. 13 is a cross-sectional view of the optical element of fig. 12 viewed in the X-X direction.

Fig. 14 is a perspective view showing an absorber of an optical element of an infrared light detector of a noninvasive blood glucose level measuring apparatus according to embodiment 1 of the present invention.

Fig. 15 is a schematic diagram showing the configuration of a noninvasive blood glucose level measuring apparatus according to embodiment 2 of the present invention.

Fig. 16 is a schematic diagram showing the configuration of a noninvasive blood glucose level measuring apparatus according to variation 1 of embodiment 2 of the present invention.

Fig. 17 is a schematic diagram showing the configuration of a noninvasive blood glucose level measuring apparatus according to variation 2 of embodiment 2 of the present invention.

Detailed Description

Hereinafter, a biological material measurement device according to an embodiment of the present invention will be described with reference to the drawings. In each embodiment, the same components are denoted by the same reference numerals, and description thereof is omitted.

Embodiment 1.

Fig. 1 is a schematic diagram showing an example of use of a noninvasive blood glucose level measuring apparatus according to embodiment 1 of the present invention, which is generally designated 80. The head (distal end) 80a of the noninvasive blood glucose level measuring apparatus 80 is brought into contact with the skin of the subject to measure the blood glucose level of the subject. The skin to be brought into contact with the head 80a of the noninvasive blood glucose level measuring apparatus 80 is preferably a thin-cornered lip, but is not limited thereto, and may be, for example, the skin of a cheek, an earlobe, a fingernail, or the like.

Fig. 2 is a schematic diagram showing the configuration of a noninvasive blood glucose level measuring apparatus 80 according to embodiment 1 of the present invention. The noninvasive blood glucose level measuring apparatus 80 includes: an infrared light source 32 that emits infrared light having a wavelength range of all or a part of the absorption wavelength range (8.5 to 10 μm) of biological substances, an ATR prism 20 through which the infrared light emitted from the infrared light source 32 passes, and an infrared light detector 30 that detects the intensity of the infrared light emitted from the ATR prism 20. The noninvasive blood glucose level measuring apparatus 80 further includes: a doubly curved metamaterial 90 formed on the head 80a of the noninvasive blood glucose level measuring apparatus 80. In other words, the doubly curved metamaterial 90 is formed on the ATR prism 20.

As the infrared light source 32, for example, a quantum cascade laser module is used. The quantum cascade laser is a single light source, has large output power and high SN ratio, so that high-precision measurement becomes possible. A quantum cascade laser module is equipped with a lens for collimating a light beam.

The infrared light emitted from the infrared light source 32 is incident on the ATR prism 20. The incident infrared light is transmitted through the ATR prism 20 while repeating total reflection, and then is emitted from the ATR prism 20. That is, schematically, the infrared light emitted from the infrared light source 32 is reflected by the end face 20c of the ATR prism 20. The reflected infrared light passes through the ATR prism 20, is reflected at the end surface 20b, then passes through the ATR prism 20 to reach the end surface 20a, passes through the doubly curved metamaterial 90, is reflected at the surface (distal end surface) of the doubly curved metamaterial 90 in contact with the skin 49 of the subject, then passes through the doubly curved metamaterial 90 and the ATR prism 20, and is reflected again at the end surface 20b of the ATR prism 20. Reflection at the surface of the doubly curved metamaterial 90 and reflection at the end face 20b of the ATR prism 20 are repeated, and infrared light reaches the end face 20d of the ATR prism 20, is reflected, and exits the ATR prism 20.

For the part of the ATR prism 20 where the infrared light exits, a non-reflective coating may be applied. Alternatively, the infrared light emitted from the infrared light source 32 may be p-polarized light, and the ATR prism 20 may be processed so that the incident angle and the exit angle of the infrared light become brewster's angle.

The material of the ATR prism 20 is, for example, a single crystal of zinc sulfide (ZnS) that is transparent to light having a wavelength in the mid-infrared region and has a relatively small refractive index. The material of the ATR prism 20 may be a known material such as zinc selenide (ZnSe). However, the material of the ATR prism 20 is not limited to these.

In order not to cause damage to the human body, the portion of the ATR prism 20 or hyperbolic metamaterial 90 that contacts the skin 49 may be coated with a coating containing SiO₂Or a thin film of SiN or the like.

The infrared light emitted from the ATR prism 20 enters the infrared light detector 30. The infrared light detector 30 is a module mounted with an uncooled measuring device such as an mems (micro Electro Mechanical systems) type measuring device or a thermopile, for example. The infrared light detector 30 includes: a circuit such as a preamplifier, and a lens for condensing the infrared light incident on the infrared light detector 30 on an element of the measurement device. Further details of the infrared light detector 30 will be described later.

The noninvasive blood glucose level measuring apparatus 80 further includes: and a control unit 52 electrically connected to the infrared light source 32 and the infrared light detector 30. The control unit 52 can control the oscillation of the infrared light source 32, the wavelength and intensity of the infrared light emitted from the infrared light source 32, and the like. Further, the control unit 52 receives the intensity data of the detected infrared light from the infrared light detector 30, and calculates the concentration of the blood glucose level in the living body based on the intensity data.

The noninvasive blood glucose level measuring apparatus 80 further includes: and a user interface 54 electrically connected to the control section. As for the user interface 54, for example, there are included: a display 501 for displaying measurement start means, measurement condition setting means, and the like to the user, a vibrator 502 and a speaker 503 for notifying the user of the measurement status (for example, start and end of measurement) by vibration and sound, respectively, and a keyboard 504 for the user to perform measurement start operation, measurement condition setting operation, and the like.

Fig. 3 shows a schematic cross-sectional view of an example of a doubly curved metamaterial 90. The doubly curved metamaterial 90 has a multilayer structure in which metal layers 91 and dielectric layers 92 are alternately stacked. The thickness of metal layer 91 and dielectric layer 92 is preferably less than 1/4 of the wavelength used. For example, when infrared light is used for detecting sugar, the thicknesses of the metal layer 91 and the dielectric layer 92 are about 10nm, respectively. In fig. 3, the doubly curved metamaterial 90 has an 8-layer structure, but the number of layers is not limited thereto.

The metal layer 91 of the doubly curved metamaterial 90 is made of a material that generates a surface plasmon in a wavelength range of light used. In a noninvasive blood glucose level measuring apparatus 80 using the wavelength of infrared light for detecting a biological substance such as sugar, the metal layer 91 of the doubly curved metamaterial 90 is, for example, gold or silver. The metal layer 91 of the doubly curved metamaterial 90 may be a layer made of a compound such as titanium nitride or graphene. In particular, in the case of using infrared light, graphene is advantageous because it is a material with small optical loss. Alternatively, the metal layer 91 of the doubly curved metamaterial 90 may be a layer composed of a semiconductor material. The semiconductor material is advantageous in that desired physical properties can be obtained by adjusting the doping concentration.

The dielectric layer 92 of the hyperbolic metamaterial 90 is preferably silicon oxide (SiO)₂) Silicon nitride (SiN), aluminum oxide (Al)₂O₃) Or magnesium fluoride (MgF)₂) However, the present invention is not limited thereto.

Fig. 4 is a schematic cross-sectional view showing another example of the doubly curved metamaterial, indicated by 95. The doubly curved metamaterial 95 comprises at least one defect layer 93 in the laminated structure of the metal layer 91 and the dielectric layer 92. In the present specification, the term "defect" means a difference in regularity from the surroundings. The thickness of the defect layer 93 is different from the thicknesses of the metal layer 91 and the dielectric layer 92. The defect layer 93 is a metal layer or a dielectric layer.

In the periodic laminated structure of the hyperbolic metamaterial, a wavelength range in which the hyperbolic metamaterial functions can be designed by adjusting the number of layers, the layer thickness, the material, and the like. In the periodic laminated structure, by introducing the defect layer 93 which disturbs the period, it is possible to confine light of a specific wavelength in the defect layer 93 or to improve the transmittance of light of a specific wavelength. For example, infrared light having a wavelength absorbed by a biological substance such as glucose is transmitted as it is, while the dispersion relation of the layered structure with respect to visible light can be made to be the dispersion relation of the hyperbolic metamaterial.

As described above, by introducing the defect layer 93, the dispersion relation of the laminated structure can be controlled according to the wavelength. In addition, the degree of freedom of measurement can be improved. Therefore, the accuracy of measurement can be improved. In embodiment 2 below, the defect layer 93 may be introduced, and the effects thereof are the same as those described above.

Fig. 5a to 5c are diagrams showing another example of the doubly curved metamaterial, indicated by 96. Fig. 5a is a top view of a doubly curved metamaterial 96. Fig. 5b is a perspective view of the doubly curved metamaterial 96. Fig. 5c is a partially sectioned perspective view showing a partial section of the doubly curved metamaterial 96 cut along line 5c-5c of fig. 5 a.

The doubly curved metamaterial 96 includes a plurality of metal rods 91a and a dielectric 92a filling the periphery of the metal rods 91 a. In the example of fig. 5a to 5c, the metal bar 91a has: the bottom surface has a circular cylindrical shape with a diameter D. Alternatively, the shape of the metal rod 91a is not limited to the cylindrical shape having a circular bottom surface, and may be a cylindrical shape having an elliptical bottom surface or a quadrangular prism shape having a square or rectangular bottom surface as long as the characteristics of the hyperbolic metamaterial are satisfied. As for the metal rods 91a, as shown in the plan view of fig. 5a, in a plan view, two-dimensionally arrayed in a radial direction with a period P. The metal rod 91a is made of a material that generates a surface plasmon in the wavelength range of light to be used, as in the metal layer 91 (see fig. 3 and 4).

The thickness D and the period P of the metal bar 91a are preferably less than 1/4 of the wavelength used. For example, when infrared light is used for detecting sugar, the thickness and the period P of the metal rod 91a are about 10nm, respectively. Fig. 5a to 5c are merely examples of the arrangement of the metal rods 91a, and the arrangement of the metal rods 91a is not limited thereto.

Fig. 6 is a plan view showing another example of the doubly curved metamaterial, indicated by 97. In the periodic structure of the hyperbolic metamaterial, the wavelength range in which the function is exhibited can be designed by adjusting the number, thickness, period, material, and the like of the metal rods 91 a. The doubly curved metamaterial 97 shown in fig. 6 includes: and a defective rod 91b which disturbs the regularity of the size, the period, etc. of the metal rod 91 a. The defective rod 91b is made of the same material as the metal rod 91a, for example, but has a different thickness E from the metal rod 91 a. In such a structure having regularity, by introducing the defective rod 91b disturbing the regularity, it is possible to confine light of a specific wavelength around the defective rod 91b or to improve the transmittance of light of a specific wavelength.

In fig. 6, a defective rod 91b as a defective region is formed by selecting a specific metal rod from among the metal rods 91a and increasing the thickness of the selected metal rod. The method of forming the defective region is not limited to this, and the defective region may be formed by, for example, changing the shape of the metal rod 91a from a cylindrical shape to a quadrangular shape, disposing the metal rod at a position that disturbs the period of the arrangement of the metal rods 91a, changing the material of the metal rod 91a, or the like.

By introducing the defect bars 91b as described above, for example, infrared light having a wavelength absorbed by a biological substance such as glucose is transmitted as it is, while the dispersion relation of the layered structure with respect to visible light can be made to be the dispersion relation of the hyperbolic metamaterial.

Next, the principle of blood glucose level measurement by the noninvasive blood glucose level measuring apparatus 80 will be described. If total reflection of infrared light occurs at the interface of the ATR prism 20 and the doubly curved metamaterial 90 and/or at the interface of the doubly curved metamaterial 90 and the skin 49, an evanescent wave is generated. The evanescent wave enters the skin 49 and is absorbed by biological substances such as sugar in the living body of the measurement subject. By thus absorbing the evanescent wave, the intensity of the infrared light is attenuated. If the biological substance is large, the evanescent wave is absorbed more, and thus the attenuation of the intensity of the infrared light becomes large.

The skin 49 is composed of an epidermis near the surface and a dermis under the epidermis. The epidermis includes, in order from the surface vicinity, the stratum corneum, the stratum granulosum, the stratum spinosum, and the stratum basale. The thicknesses thereof were about 10 μm, several μm, 100 μm and several μm, respectively. Cells are generated in the basal layer and stacked in the spinous layer. In the stratum granulosum on the spinous layer, cells die because moisture (interstitial fluid) is not reached. In the stratum corneum on the stratum granulosum, dead cells become a hardened state. Sugars and other biological substances are present in interstitial fluid in the epidermis. Interstitial fluid increases from the stratum corneum to the spinous layer. Therefore, the degree of attenuation of the totally reflected infrared light also varies depending on the length of invasion of the evanescent wave into the skin.

The intensity of the evanescent wave is attenuated exponentially in the direction from the reflecting surface to the skin, and the length of the evanescent wave penetrating into the skin is around the wavelength of infrared light. Therefore, when infrared light having a wavelength of 8.5 to 10 μm that is absorbed by sugar is used in the noninvasive blood glucose level measuring apparatus 80, the amount of sugar present at a position from the skin surface to a depth of 8.5 to 10 μm can be detected.

Next, the characteristics of the doubly curved metamaterial 90 will be described. First, generally, properties of a flat film are described. With the x and y axes perpendicular to each other, the film extends in the xy plane. The z direction is a direction perpendicular to the x axis and the y axis. Let the wave numbers in the x, y and z-axis directions be k_x、k_yAnd k_z. The dielectric constant and magnetic permeability μ are described below.

[ number 1]

[ number 2]

In the case where the material of the film is a uniaxial crystal (i.e.,_xx＝_yy≠_zzin the case of (1), is described as_xx＝_yy≡_⊥、_zz＝_∥、μ_xx＝μ_yy≡μ_⊥、μ_zz＝μ_∥Therefore, the dielectric constant and the magnetic permeability μ are described by the following formulas (3) and (4), respectively.

[ number 3]

[ number 4]

In general, the dispersion relation of light is represented by the following formula (5).

[ number 5]

Where ω is the frequency of the light and c is the speed of the light.

For a typical substance (i.e., a substance that is not a doubly curved metamaterial),_||and_⊥are equal and are positive values. Namely, the following formula (6) is satisfied.

[ number 6]

_||＝_⊥＞0…(6)

In FIG. 7, the vertical axis is k_zLet the horizontal axis be k_xAnd represents the dispersion relation of a general substance (i.e., a substance that is not a hyperbolic metamaterial). S in fig. 7 represents a hill kiosk vector. Thus, the dispersion relation expressed in the wave number space is a sphere, closed.

The electric hyperbolic metamaterial is a material satisfying the following formulae (7) and (8) or formulae (7) and (9) with respect to the above-described general material.

[ number 7]

μ_⊥＝μ_||＞0…(7)

[ number 8]

_||Is < 0 and_⊥＞0…(8)

[ number 9]

_||Is greater than 0 and_⊥＜0…(9)

therefore, the dispersion relation of the electrically hyperbolic metamaterial is hyperbolic (hyperbolic) as shown in fig. 8. Therefore, no matter how large a wave number may exist. That is, in a hyperbolic metamaterial, an evanescent wave is not attenuated.

Furthermore, in noninvasive blood glucose level measuring apparatus 80 according to embodiment 1 of the present invention, the difference in refractive index between skin 49 and hyperbolic metamaterial 90 can be reduced (index matching) by adjusting the material and layer thickness of hyperbolic metamaterial 90 that is in contact with skin 49. Therefore, when the noninvasive blood glucose level measuring apparatus 80 according to embodiment 1 of the present invention including the doubly curved metamaterial 90 is used, the length of evanescent wave penetration into the skin 49 is longer than that of a conventional blood glucose level sensor using a surface plasmon. Therefore, according to noninvasive blood glucose level measurement apparatus 80 according to embodiment 1 of the present invention, glucose in the skin can be detected with high sensitivity.

Incidentally, a hyperbola showing a dispersion relation of a hyperboloid metamaterial may not be a hyperboloid separated as shown in fig. 8 (for example, refer to "poddisclosure, a.; Iorsh, i.; Belov, p.; Kivshar, y. hyperbollic metamaterials. nature Photonics 2013,7, 948-.

Fig. 9 is a schematic diagram showing the optical paths of infrared light and evanescent waves traveling in the ATR prism 20, the doubly curved metamaterial 90 and the skin 49. If the infrared light traveling in the ATR prism 20 reaches the interface of the ATR prism 20 and the doubly curved metamaterial 90, an evanescent wave generated by total reflection at the infrared light and/or the interface propagates into the doubly curved metamaterial 90.

The thickness of the layer, the number of layers, the material, etc. of the doubly curved metamaterial 90 can be selected in terms of the penetration of the infrared light alone, the evanescent wave alone, or both into the doubly curved metamaterial 90.

As described above, since the length of the evanescent wave entering the skin 49 is long, the distance (グースハンチェン displacement, corresponding to a in fig. 9) required for the phase matching between the incident wave and the reflected wave becomes long.

Further, in the doubly curved metamaterial 90, the wavelength dependence of the reflection angle of light is larger than that of a general material. That is, when light of a wavelength to be measured and light of another wavelength are emitted from the doubly curved metamaterial 90, the difference between the emission angle of the light of the wavelength to be measured and the emission angle of the light of the other wavelength is larger than that in the case of emitting the light from a normal material. Therefore, if the infrared light detector 30 is provided at a position where light of a wavelength to be measured enters, light of other wavelengths does not enter the infrared light detector 30, and thus noise due to light of other wavelengths is not detected. Therefore, when the doubly curved metamaterial 90 is used, the SN ratio is improved, and highly accurate measurement is possible.

The doubly curved metamaterial 90 can be easily manufactured by alternately stacking a metal and an insulating layer by sputtering. In the case where graphene is used as the material of the metal layer 91 of the doubly curved metamaterial 90, graphene formed by chemical vapor deposition on a copper foil is transferred onto an insulating film. Alternatively, the graphene may be formed by a screen printing or solution coating method, or the like.

As described above, the target of measurement by the noninvasive blood glucose level measuring apparatus 80 according to embodiment 1 of the present invention is the blood glucose level. FIG. 10 shows an absorption spectrum of infrared light generated from sugar. However, the measurement target is not limited to the blood glucose level, and may be the amount of another biological substance.

Although the above description has been made of the noninvasive blood glucose level measuring apparatus 80 using infrared light, the light used is not limited to infrared light. The noninvasive blood glucose level measuring apparatus 80 can use light having a wavelength in the visible region or the THz region, for example, instead of infrared light.

As described above, by using noninvasive blood glucose level measuring apparatus 80 according to embodiment 1 of the present invention, the length of penetration of evanescent waves into the skin is longer than in conventional blood glucose level sensors, and absorption of infrared light by biological substances in the skin is increased. In addition, the distance (グースハンチェン displacement) required for phase matching between the incident wave and the reflected wave becomes large. Further, since the difference between the emission angle of light of the wavelength to be measured and the emission angle of light of another wavelength is large, light of the wavelength to be measured can be detected without detecting light of another wavelength, and high-precision measurement can be performed.

Next, the configuration of infrared light detector 30 included in noninvasive blood glucose level measuring apparatus 80 will be described in detail.

Fig. 11 is a perspective view showing an example of the configuration of the infrared light detector 30. Fig. 11 shows, for the sake of convenience of explanation, an X axis, a Y axis perpendicular to the X axis, and a Z axis perpendicular to the X axis and the Y axis. The infrared light detector 30 includes: a substrate 1 parallel to the XY plane, a sensor array 1000 disposed on the substrate, and a detection circuit 1010 disposed around the sensor array 1000. The sensor array 1000 includes: a plurality of pixels (semiconductor optical elements) 100 are arranged in a matrix (array) in 2 directions (X direction and Y direction) orthogonal to each other. In fig. 11, there are 54 (9 × 6) optical elements 100 shown. The detection circuit 1010 processes signals detected by the respective optical elements 100. The detection circuit 1010 may detect an image by processing a signal detected by the optical element 100. In noninvasive blood glucose level measuring apparatus 80, infrared light detector 30 is disposed as follows: the infrared light is incident perpendicularly (from a direction parallel to the Z-axis) to the light elements 100 of the sensor array 1000.

The optical element 100 is, for example, a thermal infrared sensor.

Fig. 12 is a top view of the optical element 100. In fig. 12, a protective film, a reflective film, and an absorber described later on the wiring are omitted to clearly show the structure of the optical element 100. Fig. 13 is a cross-sectional view of the optical element 100 of fig. 12 viewed in the X-X direction. Fig. 13 shows the absorbent body 10 in an omitted manner.

As shown in fig. 13, a hollow portion 2 is provided on a substrate 1. A temperature detection unit 4 for detecting temperature is disposed in the hollow portion 2. The temperature detection unit 4 is supported by 2 support legs 3. The support leg 3 has a bridge shape folded in an L shape if viewed from above, as shown in fig. 2. The support leg 3 includes: thin-film metal wiring 6, and dielectric film 16 supporting thin-film metal wiring 6.

The temperature detection unit 4 includes a detection film 5 and a thin-film metal wiring 6. The detection film 5 is formed of, for example, a diode using crystalline silicon, and changes in resistance according to temperature. The thin-film metal wiring 6 electrically connects the aluminum wiring 7 covered with the insulating film 12 to the detection film 5. The thin-film metal wiring 6 is made of, for example, a titanium alloy having a thickness of about 100 nm. The electric signal output from the detection film 5 propagates to the aluminum wiring 7 via the thin-film metal wiring 6 formed on the support leg 3, and is taken out by the circuit under test 1010 (fig. 11). The electrical connection between the thin-film metal wiring 6 and the detection film 5 and between the thin-film metal wiring 6 and the aluminum wiring 7 can be performed via a conductor (not shown) extending in the vertical direction as necessary.

The infrared-reflecting film 8 is disposed so as to cover the hollow portion 2. However, the reflective film 8 is not thermally connected to the temperature detection unit 4. The reflective film 8 is disposed so as to cover at least a part of the upper side of the support leg 3.

Above the temperature detecting section 4, a support 9 is provided to support the absorber 10 thereon. That is, the absorber 10 and the temperature detection unit 4 are thermally connected by the support 9. Therefore, the temperature change generated in the absorber 10 is transmitted to the temperature detection unit 4. An absorption preventing film 13 for preventing absorption of light from the back surface is provided on the back surface of the absorber 10, that is, on the side of the support 9. A metal film (metal film 42 in fig. 14) described later is provided on the surface of the absorber 10, but is not shown in fig. 13.

On the other hand, the absorber 10 is disposed above the reflective film 8 and is not thermally connected to the reflective film 8. The absorber 10 is extended in a plate shape laterally (in the XY direction) to cover and hide at least a part of the reflective film 8. Therefore, as shown in fig. 14 described later, when the optical element 100 is viewed from above, only the absorber 10 is seen. Alternatively, the absorbent body 10 may be formed directly above the temperature detection unit 4.

Fig. 14 is a perspective view showing the absorber 10 of the optical element 100. The absorber 10 includes a wavelength selective structure 11 on the surface thereof, which selectively absorbs light of a specific wavelength. Since the wavelength selective structure 11 may absorb light, the wavelength selective structure 11 is referred to as an absorber 10.

The optical element 100 uses surface plasmons in the wavelength selective structure 11. When a periodic structure made of metal is provided on the light incident surface, if light having a wavelength corresponding to the surface periodic structure is incident, surface plasmons are generated, and light absorption occurs. By using this, the surface of the absorber 10 is formed of metal, and the wavelength of the incident light, the incident angle, and the pitch p of the periodic structure of the metal surface are adjusted, whereby the wavelength of the light absorbed by the absorber 10 can be selected.

In the present specification, the generation of a surface mode attributed to free electrons in the metal film when light is incident and the generation of a surface mode attributed to a periodic structure are considered synonymous from the viewpoint of light absorption, and are referred to as a surface plasmon, a surface plasmon resonance, or simply a resonance without distinguishing them from each other. The phenomenon is also referred to as a quasi-surface plasmon or a metamaterial, and the essential phenomenon related to absorption is the same, and therefore, they are not distinguished.

The wavelength selection structure 11 includes: a main body 43, a metal film 42 formed on the main body 43, and a plurality of recesses 45 periodically provided on the main body 43. The material of the metal film 42 is selected from metals such as Au, Ag, Cu, Al, Ni, and Mo that generate surface plasmon resonance. The material of the metal film 42 may be metal nitride such as TiN, metal boride, metal carbide, or the like, which generates surface plasmon resonance.

The thickness of the metal film 42 may be any thickness that does not allow incident light to pass therethrough. This is because, if the film thickness of the metal film 42 is such a thickness, only the surface plasmon resonance at the surface of the absorber 10 affects the absorption and radiation of the electromagnetic wave, and the material under the metal film 42 does not optically affect the absorption and radiation. The thickness through which the incident light is not transmitted is correlated with the thickness (skin depth)1 of the skin effect represented by the following formula (10). That is, if the thickness of the metal film 42 is 2 times (for example, 10nm to several 100nm) or more as large as 1, almost no incident light transmits through the metal film 42. Therefore, the leakage of the incident light to the lower side of the absorber 10 can be sufficiently reduced.

[ number 10]

1＝(2/μσω)^1/2…(10)

Where μ denotes the magnetic permeability of the metal film 42, σ denotes the electrical conductivity of the metal film 42, and ω denotes the angular vibration number of incident light.

The main body 43 of the wavelength selective structure 11 is made of a dielectric or a semiconductor. For example, the main body 43 of the wavelength selective structure portion 11 is made of silicon oxide (SiO)₂) And (4) forming. The metal film 42 is made of gold, for example. Since the heat capacity of silicon oxide is smaller than that of gold, the absorber 10 having the body 43 made of silicon oxide and the metal film 42 made of gold is provided withAn absorber made of gold alone has a smaller heat capacity than an absorber made of gold alone. As a result, the response of the optical element 100 can be accelerated. Further, the cost can be reduced as compared with an absorber made of a metal such as gold alone.

The concave portion 45 of the wavelength selective structure portion 11 has, for example, a cylindrical shape with a diameter of 4 μm and a depth of 1.5 μm. In the wavelength selective structure 11, the columnar recesses 45 are arranged in a square lattice pattern with a period (pitch) of 8 μm. In this case, the wavelength of the light absorbed by the absorber 10 is about 8 μm. The cylindrical recesses 45 may be arranged in a square lattice shape with a period of 8.5 μm. In this case, the wavelength of the light absorbed by the absorber 10 is about 8.5 μm.

The following are found: the relationship between the wavelength of light absorbed by the absorber 10 (hereinafter referred to as "absorption wavelength") and the wavelength of light emitted from the absorber 10 (hereinafter referred to as "emission wavelength") and the period p of the recesses 45 is substantially the same between the case where the recesses 45 are arranged in a square lattice pattern and the case where the recesses are arranged in a two-dimensional periodic structure other than the square lattice pattern. That is, in all cases, the absorption wavelength and the emission wavelength are determined by the period p of the concave portion 45.

In this regard, theoretically, if the reciprocal lattice vector of the periodic structure is considered, in the square lattice configuration, the absorption wavelength and the emission wavelength are substantially equal to the period p, and in the triangular lattice configuration, the absorption wavelength and the emission wavelength are considered to be the period p × √ 3/2. However, in practice, the absorption wavelength and the emission wavelength slightly vary depending on the diameter d of the concave portion 45, and it is considered that all the two-dimensional periodic structures absorb or emit light having a wavelength substantially equal to the period p.

Therefore, the arrangement of the concave portions 45 is not limited to the square lattice shape, and may be a two-dimensional periodic structure other than the square lattice shape such as a triangular lattice shape.

As described above, the wavelength of light absorbed by the absorber 10 can be controlled by adjusting the period p of the concave portions 45. The diameter d of the concave portion 45 is preferably 1/2 or more of the period p in general. In the case where the diameter d of the concave portion 45 is smaller than 1/2 of the period p, the resonance effect becomes small, and the absorption rate of incident light tends to decrease. However, since the resonance is three-dimensional resonance in the concave portion 45, sufficient absorption may be obtained even if the diameter d is smaller than 1/2 of the period p. Therefore, the value of the diameter d with respect to the period p can be appropriately designed separately. It is important that the absorption wavelength is mainly determined by the period p, and therefore, the period p can be adjusted to control the absorption wavelength. If the diameter d is equal to or larger than a certain value with respect to the period p, the absorbent body 10 has sufficient absorption characteristics. Therefore, the design conditions of the absorber can be flexibly determined.

On the other hand, from the dispersion relation of the surface plasmon, it is known that: the light absorbed by the absorber 10 is independent of the depth of the recesses 45 and depends only on the period p.

The absorbent body 10 in which the concave portions 45 are periodically arranged has been described above. However, in the wavelength selective structure 11 of the absorber 10, convex portions protruding from the surface may be periodically arranged. Even with such a configuration, the same effects as described above can be obtained.

In addition, the concave portion 45 has a cylindrical shape as described above, and the shape of the concave portion 45 may be rectangular or elliptical as viewed from the top surface, for example. The arrangement of the concave portions 45 is not limited to the two-dimensional periodic arrangement, and may be, for example, a one-dimensional periodic arrangement. In these cases, the absorption of the incident light depends on the polarization of the incident light. For example, when the light emitted from the light source has a polarization, the absorber 10 can be designed to absorb only the polarization. This can improve the SN ratio.

In the absorption of the incident light by the absorber 10, the absorption becomes maximum when the incident light is made incident perpendicularly to the absorber. When the angle of incidence on the absorber 10 deviates from the perpendicular, the absorption wavelength changes, and the absorption rate of the incident light also decreases.

Next, a method for producing the absorbent body 10 will be described. On the surface of the body 43 made of a dielectric or a semiconductor, periodic recesses 45 are formed by photolithography and dry etching. Then, on the entire surface of the body 43 including the concave portion 45, the metal film 42 is formed by sputtering or the like. Similarly, a metal film 42 is also formed on the back surface. Since the diameter d of the concave portion 45 illustrated in the drawings is as small as about several μm, the step of forming the metal film 42 after etching the body 43 to form the concave portion 45 can be performed more easily than the step of directly etching the metal film 42 to form the concave portion.

Embodiment 2.

Fig. 15 is a schematic diagram showing the configuration of a noninvasive blood glucose level measuring apparatus according to embodiment 2 of the present invention, which is shown as a whole at 81. The noninvasive blood glucose level measuring apparatus 81 includes: an infrared light source 32 that emits infrared light having a wavelength range of all or a part of the absorption wavelength range (8.5 μm to 10 μm) of biological substances, an ATR prism 20 through which the infrared light emitted from the infrared light source 32 passes, a doubly curved metamaterial 90 formed on the ATR prism 20, a control unit not shown, and a user interface not shown. Fig. 15 is a diagram of a non-invasive blood glucose level measuring apparatus 81 in which a hyperboloid metamaterial 90 on the head is in contact with the skin 49 of a subject.

The noninvasive blood glucose level measuring apparatus 81 according to embodiment 2 of the present invention further includes: a visible light source 71 that emits visible light to the ATR prism 20, and a visible light detector 72 that detects the intensity and position of the visible light transmitted and emitted from the ATR prism 20.

The visible light emitted from the visible light source 71 is incident on the ATR prism 20. The incident visible light passes through the ATR prism 20 while repeating total reflection, and then exits the ATR prism 20 to enter the visible light detector 72.

The infrared light emitted from the infrared light source 32 reaches the skin 49 of the measurement subject via the ATR prism 20 and the doubly curved metamaterial 90. The infrared light is absorbed by biological substances (e.g., glucose) within the skin 49, thereby generating heat. The temperature of the ATR prism 20 rises due to the generated heat. As the temperature rises, the optical constants such as the refractive index of the ATR prism 20 change, and the emission angle of the visible light emitted from the ATR prism 20 changes. The position where the visible light reaches changes due to the change in the emission angle. Therefore, the position where the visible light reaches is detected by the visible light detector 72, and the generated heat can be determined from the change in the optical constant of the ATR prism 20. That is, the more the amount of the biological substance is, the more the absorption amount of the visible light is, and the more the absorption amount is, the more the generated heat is increased. Therefore, as the amount of the biological material increases, the change in the emission angle of the visible light emitted from the ATR prism 20 increases. In this way, the amount of biological matter within the skin 49 can be determined.

When the optical elements of the visible light detector 72 are single pixels, the arrival position of the emitted light is found by mechanical scanning, and the change in the emission angle of the visible light from the ATR prism 20 can be calculated.

As described above, the amount of the biological substance can be determined using the heat generated by absorbing the infrared light. This method is called an optical/thermal method.

In such a measurement device, by forming the doubly curved metamaterial 90 on the ATR prism 20, the change in the emission angle of the visible light from the ATR prism 20 can be made larger. In the case where the doubly curved metamaterial 90 is provided on the ATR prism 20, an evanescent wave generated by the total reflection of the visible light incident to the ATR prism 20 and/or the visible light at the interface of the ATR prism 20 and the doubly curved metamaterial 90 passes within the doubly curved metamaterial 90. The optical constants such as the refractive index of the doubly curved metamaterial 90 vary depending on the temperature. In particular, when the doubly curved metamaterial 90 is used, the temperature dependence of the change in the emission angle of visible light is large as compared with the case of using a substance having a normal dispersion relation. Therefore, by using the doubly curved metamaterial 90, the emission angle of visible light can be changed more greatly. That is, even if the amount of absorption of visible light by a biological substance is small, the change in the emission angle can be made large, and thus the measurement accuracy is improved.

< modification 1 >

Fig. 16 is a schematic diagram showing the configuration of a noninvasive blood glucose level measuring apparatus according to modification 1 of embodiment 2 of the present invention, which is generally designated 82. In modification 1 of embodiment 2 of the present invention, the visible light detector 72 includes: a plurality of pixels (semiconductor optical elements) 73 are arranged in a matrix (array) in 2 directions orthogonal to each other.

By forming the visible light detector 72 into an array, the intensity of visible light can be detected for each pixel 73. Therefore, the position where the amount of visible light is maximum can be found in detail. This enables the emission angle of the visible light from the ATR prism 20 to be detected with high accuracy. Therefore, the amount of heat generated, that is, the amount of biological material can be measured with high accuracy from the amount of change in the emission angle.

In fig. 16, 12 pixels 73 are shown, but the number of pixels 73 is not limited to this. The visible light detector 72 may be an image sensor.

< modification 2 >

Fig. 17 is a schematic diagram showing the configuration of a noninvasive blood glucose level measuring apparatus according to modification 2 of embodiment 2 of the present invention, which is indicated as a whole by 83. In modification 2 of embodiment 2 of the present invention, the visible light source 71 includes: the plurality of light source elements 74 are arranged in a matrix (array) in 2 directions orthogonal to each other.

The plurality of light source elements 74 may emit visible light of the same wavelength. Since the plurality of light source elements 74 are disposed at different positions, the visible light emitted from each light source element 74 enters the ATR prism 20 at different positions or incident angles. Therefore, the visible light emitted from each light source element 74 is incident on a different position of the skin 49. Since the influence of temperature varies depending on the incident position on the skin 49, the change in the emission angle of each visible light from the ATR prism 20 due to temperature varies. By calculating the change in the emission angle due to the difference in the incident positions of the visible light, the measurement accuracy can be improved.

Unlike the above, at least one of the plurality of light source elements 74 may emit visible light of a different wavelength from the other light source elements 74. By calculating the change in the emission angle due to the difference in the wavelength of the visible light, the measurement accuracy can be improved.

In modification 2 of embodiment 2 of the present invention, too, the use of the doubly curved metamaterial 90 enables the emission angle of visible light to be changed more greatly. That is, even if the amount of absorption of visible light by a biological substance is small, the change in the emission angle can be increased, and thus the measurement accuracy is improved.

Description of reference numerals

10 absorbers, 11 wavelength selection structure part, 20 ATR prism, 30 infrared photodetector, 32 infrared light source, 52 control part, 54 user interface, 71 visible light source, 72 visible light detector, 74 light source element, 80 noninvasive blood glucose level measuring device, 90 hyperbolic metamaterial, 91 metal layer, 92 dielectric layer, 93 defect layer, 100 optical element, 1000 sensor array, 1010 detection circuit.

Claims

1. A biological material measurement device is provided with:

a first light source that emits first light,

an ATR prism having a front surface and a back surface, the first light incident from one end being transmitted through the inside and being emitted from the other end,

a doubly curved metamaterial layer having a surface and a back surface, disposed in contact with said back surface on the surface of said ATR prism, and

a first photodetector that detects the first light emitted from the ATR prism,

determining the amount of the biological substance in the organism from the detected first light.

2. The biological substance measurement device according to claim 1, wherein the first light incident to the ATR prism is reflected at a back surface of the ATR prism and a surface of the ATR prism and/or a surface of the doubly curved metamaterial layer, and is transmitted through the ATR prism,

contacting the doubly curved metamaterial layer with a biological body, and determining an amount of a biological substance in the biological body from an amount of the first light absorbed by the biological body.

3. The biological substance assay device according to claim 1 or 2, wherein the first photodetector has on its surface: a plurality of recesses or projections arranged at a constant period in 1 direction or 2 directions intersecting each other while being spaced apart from each other, and having at least a surface made of a metal,

the predetermined period is a period in which a surface plasmon is generated in the concave portion or the convex portion by the incidence of the first light.

4. The biological substance measurement device according to any one of claims 1 to 3, wherein the first light source, the ATR prism, the first photodetector, and the doubly curved metamaterial layer are arranged such that the first light emitted from the ATR prism is incident perpendicularly to a surface of the first photodetector.

5. The biological substance measurement device according to any one of claims 1 to 4, wherein the first light is infrared light.

6. The biological substance measurement device according to claim 1 or 2, further comprising: a second light source for emitting a second light,

the first light incident on the ATR prism is reflected by the rear surface of the ATR prism and the surface of the ATR prism and/or the surface of the doubly curved metamaterial layer, and is transmitted through the ATR prism,

the second light is irradiated to the living body in a state where the hyperbolic metamaterial layer is in contact with the living body, and the amount of the biological substance is measured by a change in the first light caused by heat generated by the biological substance in the living body absorbing the second light.

7. The biological substance measurement device according to claim 6, wherein the change in the first light is: a change in the exit angle of the first light caused by the thermally-induced change in the refractive index of the ATR prism and/or the doubly curved metamaterial layer.

8. The biological substance measurement device according to claim 6 or 7, wherein the first photodetector is a plurality of first photodetectors arranged at different positions,

calculating the amount of the biological substance using the intensity and the position data of the respective first lights at the different positions.

9. The biological substance measurement device according to any one of claims 6 to 8, wherein the first light is visible light and the second light is infrared light.

10. The biological substance measuring device according to any one of claims 6 to 9, wherein the first light source is a plurality of first light sources that emit first light having different wavelengths from each other.

11. The biological substance measurement device according to any one of claims 1 to 10, wherein the hyperbolic metamaterial layer has a structure in which metal layers containing metal and dielectric layers are alternately stacked.

12. The bio substance assay device according to claim 11, wherein the number of layers, thickness, and material of the hyperbolic metamaterial layer are determined such that surface plasmon resonance is generated by the first light incident to the hyperbolic metamaterial layer.

13. The bio material assay device according to claim 11 or 12, wherein the number of layers, thickness and material of the hyperbolic metamaterial layer are determined such that optical constants of the hyperbolic metamaterial layer vary according to a temperature change.

14. The biological substance assay device according to any one of claims 11 to 13, wherein a thickness of the metal layer and/or a thickness of the dielectric layer of the doubly curved metamaterial layer is less than 1/4 of a wavelength of the first light.

15. The biological substance assay device according to any one of claims 11 to 14, wherein at least one of the metal layer and the dielectric layer of the doubly curved metamaterial layer has a thickness different from a thickness of the other layers, and the thickness of the other layers is equal.

16. A biological substance assay device according to any one of claims 1 to 10, wherein the doubly curved metamaterial layer comprises: a metal rod having a columnar shape with the thickness direction of the hyperbolic metamaterial layer as a central axis; and a dielectric filling a periphery of the metal rod in a radial direction perpendicular to the central axis.

17. The bio substance assay device according to claim 16, wherein metal rods of the hyperbolic metamaterial layer are periodically arranged one-dimensionally or two-dimensionally in the radial direction, and a thickness, an arrangement period, and a material of the metal rods are determined such that surface plasmon resonance is generated by the first light incident to the hyperbolic metamaterial layer.

18. The bio material assay device according to claim 16 or 17, wherein the metal rods of the hyperbolic metamaterial layer are periodically arranged one-dimensionally or two-dimensionally in the radial direction, and the thickness, the period of arrangement, and the material of the metal rods are determined such that the optical constants of the hyperbolic metamaterial layer vary according to a temperature change.

19. A biological substance assay device according to any one of claims 16 to 18, wherein the metal rods of the doubly curved metamaterial layer have a thickness and/or a period of arrangement that is less than 1/4 of the wavelength of the first light.

20. A biological substance measuring device according to any one of claims 16 to 19, wherein at least one of the metal rods has a thickness different from that of the other metal rods.

21. A biological substance assay device as claimed in any one of claims 11 to 20, wherein the metal comprises graphene.